Cesarean Scar Pregnancy: A Three-Year Experience at Yale-New Haven Hospital [2N]

INTRODUCTION:The incidence of cesarean scar pregnancy (CSP) is rising along with the cesarean delivery rate. Data on the optimal management of the CSP are limited. METHODS:This is a series of all CSP cases diagnosed over the period 5/2013–8/2016 at Yale-New Haven Hospital. Data were collected retrospectively and prospectively from electronic medical records with approval from the Institutional Review Board. RESULTS:Sixteen cases of CSP were diagnosed in 14 patients, including 2 recurrences. Median number of prior cesarean deliveries was 3 (SD 0.98). Median gestational age at time of diagnosis was 45.5 days (6+3/7 weeks) (SD 11). Fetal cardiac activity was detected in 10 cases. Three patients had spontaneous demise of the CSP and were managed expectantly. Others opted for termination via systemic methotrexate alone (n=4); combined systemic/local methotrexate (n=5); systemic/local methotrexate with bilateral uterine artery embolization (n=1); systemic/local methotrexate with intra-sac KCl injection (n=2); and KCl injection with laparotomy and wedge resection (n=1). Three patients who underwent expectant management or methotrexate therapy had retained products of conception diagnosed 48, 61 and 82 days after initial diagnosis that required hysteroscopy and curettage. One patient opted for hysterectomy after curettage for definitive management. Three patients spontaneously conceived after resolution of CSP. Two patients had recurrences that were managed with methotrexate therapy. One patient has an ongoing viable intrauterine gestation. CONCLUSION:This case series highlights the risk of complications associated with expectant management and methotrexate therapy, and demonstrates the potential for spontaneous conception following CSP

Relationships of maternal serum levels of vascular endothelial growth factor and tensile strength properties of the cervix in a rat model of chronic hypoxia

It has been shown that hypoxia leads to alterations in maternal serum levels of vascular endothelial growth factor (VEGF). In this study, we sought to test the hypothesis that chronic hypoxia increases maternal serum levels of VEGF, which in turn cause measurable changes in the viscoelastic properties of the rat uterine cervix. Timed-pregnant adult Sprague-Dawley rats were exposed to hypoxia beginning on day 17 of gestation (term = day 22). The following groups of animals were studied: (1) nonpregnant controls (NP, n = 6); (2) normoxia 21% fraction of inspired oxygen (FiO 2) (NMX, n = 6); and (3) severe hypoxia 10% FiO 2 (HPX; n = 5). A hypoxic chamber was used to assure consistent hypoxic environment. Animals were killed on day 21 of gestation (before labor). Maternal blood was collected immediately following anesthesia and prior to euthanasia. Free serum levels of VEGF were measured by highly specific immunoassays. Tensile strength properties of the cervix were assessed using a stretching regimen designed to mimic labor. Physical parameters measured were: indicators of viscoelasticity (slope; measure of stiffness), plasticity (yield point [YP]; moment the tissue changes its properties from elastic to plastic), strength (break point [BP]; moment of tissue disruption), and displacement at YP (marks the duration of the viscoelastic phase of the stretching) and BP (a measure of the strength of the material). Data were normalized to the dry weight of the cervix. Hypoxia is associated with increased serum levels of VEGF compared to NP or NMX groups ( P = .001). Cervical stiffness was lower in NMX, compared with NP animals ( P = .004), and was not significantly influenced by hypoxia ( P > .05). Overall there was a significant inverse correlation between slope and maternal serum levels of VEGF (r = −0.85, P < .001). The force required to reach YP was significantly higher for the NP, compared with NMX and HPX groups ( P = .004). Hypoxia did not alter the force required to reach the YP (NMX vs HPX, P > .05). Conversely, hypoxia significantly decreased the displacement at YP, indicating a shortening of the elastic phase (NMX vs HPX, P = .021). There was a significant inverse correlation between maternal serum levels of VEGF and the displacement at YP (r = −0.68, P = .002). In vivo, hypoxia decreased the force required to reached the BP (NMX vs HPX, P = .025), but there was no correlation between the levels of maternal serum VEGF and this indicator (r = −0.35, P = .170). Chronic hypoxia induces measurable changes in maternal serum levels of VEGF and tensile properties of the rat cervix, specifically a shortening of the elastic phase. Hypoxia decreases the cervical strength to stretch and predisposes to rupture, but this effect seems to be unrelated to maternal serum levels of VEGF

Cesarean Scar Pregnancy, Incidence, and Recurrence Five-Year Experience at a Single Tertiary Care Referral Center

OBJECTIVE: To describe the treatment and subsequent pregnancy outcomes in patients with cesarean scar pregnancies at a single institution over 5 years. METHODS: This is a case series of all cesarean scar pregnancies diagnosed from May 2013 to March 2018 at Yale-New Haven Hospital. Data were collected on each patient using electronic medical record review and included patient demographics; medical, surgical, and obstetric history; pregnancy characteristics; treatment modalities used; response to therapy; complications; and subsequent pregnancy outcomes. RESULTS: Thirty cases of cesarean scar pregnancies were diagnosed in 26 patients, including one recurrence in one patient and three recurrences in another. Forty-six percent of cesarean scar pregnancies were in Hispanic women. The median number of prior cesarean deliveries was two. Mean gestational age at the time of diagnosis was 46 days (SD +/- 10). Fetal cardiac activity was detected in 18 cases. Three patients initially were erroneously diagnosed with a viable intrauterine pregnancy and failed medical termination. Others opted for termination through systemic methotrexate alone (n=4), systemic and local methotrexate (n=12), systemic and local methotrexate with potassium chloride injected into the gestational sac (n=3), potassium chloride injection with laparotomy and wedge resection (n=1), methotrexate with bilateral uterine artery embolization (n=2), or intrauterine balloon (n=4). Five patients who underwent expectant management or methotrexate therapy had retained products of conception and required hysteroscopy and curettage. One patient opted for hysterectomy after failed curettage. After complete resolution of cesarean scar pregnancies, there were 10 subsequent spontaneous conceptions in eight patients, including four recurrent cesarean scar pregnancies, four term pregnancies, and one spontaneous abortion. One viable normally located pregnancy is ongoing. CONCLUSION: There is a wide array of treatment modalities available for cesarean scar pregnancies. Women with a cesarean scar pregnancy are at risk for its recurrence in the future, although normal pregnancy after a cesarean scar pregnancy is also possible. Safe outcomes depend on timely diagnosis and multidisciplinary care by skilled clinicians

Utility of routine screening fetal echocardiogram in pregnancies conceived by in vitro fertilization

To study the incidence and clinical significance of congenital heart defects (CHDs) detected by fetal echocardiography in pregnancies conceived by in vitro fertilization (IVF). Cohort study comparing a prospectively maintained database of all fetal echocardiograms from 2012 to 2018 and pooled data from the Connecticut Birth Defects Registry and statewide hospital discharge data. Large tertiary care center. A total of 181,749 live births and 9,252 fetal echocardiograms were analyzed. Fetal echocardiograms in patients with a previous child with a CHD, a family history of CHD, medication exposure, diabetes, anomaly in previous pregnancy, cardiac or other abnormality noted on previous ultrasound, or monochorionic twins were excluded from the final analysis. Treatment with IVF. Incidence of CHD and odds ratios with 95% confidence intervals (CIs). Infant outcomes for cases of CHD were evaluated for clinically significant disease, defined a priori as disease requiring any medical or surgical intervention or continued follow-up with pediatric cardiology. Fetal echocardiography was performed in 2,230 IVF pregnancies, of which 2,040 were without other known risk factors for CHD. The mean gestational age at the time of fetal echocardiography was 22.2 ± 1.4 weeks. The odds ratio for CHD in the IVF group compared with statewide population rates was 1.4 (95% CI 0.9–2.1). CHD was diagnosed in 26 fetuses, of which 21 were clinically insignificant ventricular septal defects. One fetal echocardiogram was concerning for pulmonary stenosis that was not present at birth. Four defects were clinically significant, indicating that 510 fetal echocardiograms were performed for every diagnosis of one clinically significant CHD in the IVF group. The incidence of CHD in IVF pregnancies without other risk factors is not significantly different from baseline population rates, and most CHDs diagnosed by fetal echocardiography in this group are clinically insignificant. Routine screening with fetal echocardiography in all IVF pregnancies provides limited utility beyond routine prenatal care and need not be recommended without the presence of other risk factors. Utilidad del screening ecocardiográfico fetal rutinario en embarazos concebidos con Fecundación in Vitro. Estudiar la incidencia y significado clínico de los defectos cardíacos congénitos (CHDs) detectados por ecocardiografía fetal en embarazos concebidos con fecundación in vitro (IVF). Estudio de cohortes comparando una base de datos mantenida prospectivamente de todas las ecocardiografías fetales entre 2012 y 2018 y los datos recopilados del Connecticut Birth Defects Registry y los datos de alta hospitalaria de todo el estado. Centro hospitalario terciario de gran tamaño. Se analizaron un total de 181,149 nacidos vivos y 9,252 ecocardiografías fetales. Se excluyeron del análisis final las ecocardiografías fetales de pacientes con un hijo previo con CHD, historia familiar de CHD, exposición a fármacos, diabetes, malformaciones en embarazos previos, malformaciones cardíacas u otras malformaciones detectadas en ecografías previas y gemelos monocoriónicos. Tratamiento de IVF. Incidencia de CHD y odds ratios con intervalos de confianza (CIs) del 95%. Los resultados de los casos de niños con CHD se evaluaron para enfermedad clínicamente significativa, definida a priori como enfermedad que requería cualquier intervención médica o quirúrgica o seguimiento continuado por cardiología pediátrica. Se realizó ecocardiografía fetal en 2,230 gestaciones de FIV, de las cuales 2,040 no tenían otros factores de riesgo conocidos para CHD. La edad gestacional media en el momento de la ecocardiografía fetal fue de 22.2 ± 1.4 semanas. La odds ratio para CHD en el grupo de IVF comparado con las tasas generales del estado fue de 1.4 (95% CI 0.9-2.1). Se diagnosticó CHD en 26 fetos, de los cuales 21 fueron defectos del septo ventricular clínicamente insignificantes. Una ecocardiografía fetal se refería a estenosis pulmonar que no se detectó en el nacimiento, Cuatro defectos eran clínicamente relevantes, indicando que se realizaron 510 ecocardiografías fetales para cada diagnóstico de una CHD clínicamente significativa en el grupo de IVF. La incidencia de CHD en embarazos de IVF sin otros factores de riesgo no es significativamente diferente de las tasas basales de la población general y la mayoría de CHDs diagnosticadas por ecocardiografía fetal en este grupo no son clínicamente relevantes. El screening rutinario de todos los embarazos de IVF con ecocardiografía fetal es poco útil más allá de los cuidados prenatales de rutina y no debería recomendarse sin la presencia de otros factores de riesgo. Defectos congénitos, patología cardíaca congénita, screening fetal, fecundación in vitro

Multidimensional system biology: Genetic markers and proteomic biomarkers of adverse pregnancy outcome in preterm birth

Premature birth before 37 weeks of gestation is a significant public health problem. Each year, 4.5 million premature infants are born worldwide. Despite extensive research and a variety of interventions, the rate of preterm birth has steadily increased over the past 20 years and reached a high of 12.8% in 2006. The etiology of most preterm births remains elusive and is likely multifactorial, with many pathophysiological pathways involved, such as excessive stretching, oxidative stress, decidual hemorrhage, and infection. Genomics and proteomics have emerged to provide a better comprehension of the pathophysiological conditions leading to preterm birth, thereby providing a perspective for improving neonatal outcome

Using proteomic analysis of the human amniotic fluid to identify histologic chorioamnionitis

OBJECTIVE: To estimate the relationship between histologic chorioamnionitis and four amniotic fluid proteomic biomarkers characteristic of inflammation (defensins 2 and 1, calgranulins C and A). METHODS: One hundred fifty-eight women with singleton pregnancies had a clinically indicated amniocentesis to rule out inflammation and infection in the context of preterm labor or preterm premature rupture of membranes. A proteomic fingerprint (Mass Restricted score) was generated from amniotic fluid using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The Mass Restricted score ranges from 0 to 4 (none to all four biomarkers present) in direct relationship with severity of intra-amniotic inflammation. Presence or absence of biomarkers was analyzed in relationship to placental pathology. Criteria for severity of histologic chorioamnionitis were 3 stages and 4 grades of inflammation of the amnion, choriodecidua and chorionic plate. RESULTS: The prevalence of histologic chorioamnionitis was 64% (stage I 12 /0, stage II 16%, and stage III 37%). The Mass Restricted score significantly correlated with stages of histologic chorioamnionitis (r=0.539, P<.001), grades of choriodeciduitis (r=0.465, P<.001), and amnionitis (r=0.536, P<.001). African-American women were overrepresented in the group with severe inflammation (Mass Restricted score 3-4, P=.022). Of the four biomarkers of the Mass Restricted score, calgranulin C had the strongest relationship with presence of stage III chorioamnionitis, independent of race, amniocentesis-to-delivery interval, and gestational age. CONCLUSION: Proteomic analysis of amniotic fluid provides an opportunity for early recognition of histologic chorioamnionitis. This methodology may in the future identify candidates for antenatal therapeutic interventions

Fetal interventions in the setting of the coronavirus disease 2019 pandemic: statement from the North American Fetal Therapy Network

status: publishe